MOTO T-Cell kurapwa kubvumidzwa uye kuwanikwa

July 2021: Muna June 2014, KITE Biotechnology Company, ine vashandi 19 chete, yakanyorwa paNASDAQ muUnited States, uye yakatora mamiriyoni 130 emadhora ekuAmerica muzuva rimwe chete! Mwedzi miviri chete gare gare, Juno Biotechnology yakanga ine vashandi vasingasviki makumi maviri. Kambani yakazivisa kuti yakabudirira kukwidza mamiriyoni 20 emadhora emadhora mumari imwe chete, saka Juno yakasimudza vanopfuura mamiriyoni mazana matatu mugore rimwe! Aya makambani madiki maviri haana mari uye haana madhiragi akanyorwa, saka nei achinyanya kufarirwa nevaisiri mari uye aine mari inotumirwa kwavari? Nekuti vakagona hunyanzvi hunonzi CAR-T cell therapy, tekinoroji inogona kurapa gomarara! Mazuva ano, iyo yakakurumbira CAR-T inotaurwa, anenge munhu wese anoziva izvi, Immunotherapy yakapinda zviri pamutemo mumakiriniki.

FDA yakabvumidza maviri ekurapa kweCAR-T

Currently, two CAR T-cell therapies approved by the FDA, Yescarta and Kymriah, are used to treat leukemia and lymphoma, maererano.

Aya marapirwo akaratidzirwa kukurudzira mhinduro dzakakosha-kunyangwe varwere vekenza vemberi vanorarama kwemwedzi mishoma vanogona kupedzwa zvachose, uye mune dzimwe nguva vanopindura zvine simba kwemwedzi kana kunyange makore.

Semuenzaniso, Emily, musikana weleukemia, akarapwa zvinobudirira neCAR-T cell therapy kwemakore manomwe. Iye ave zvakare mutauriri weiyi epic kurapa uye akanyorwa munhoroondo.

Chishamiso cheCAR T-Cell kurapwa

EMILY - LEUKEMIA GIRL 2019

Dr. CARL JUNE - MUDZIDZISI WECAR T-CELL THERAPY

Chii chinonzi CAR T Cell Therap?

Iyi kurapa inoparadzanisa immune T masero kubva kuvarwere, uye genetiki mainjiniya aya masero mu vitro, achiaisa iwo ne "chimeric antigen receptors" (CARs) ayo anoziva cancer cancer cell antigen. Shure kwaizvozvo, aya maseru akashandurwa anoenda mukuwedzera kuwanda murabhoritari isati yadzoserwa mumurwere. Ikoko, vaive vakaita seuto rakanyatsodzidziswa rakashongedzerwa nezvombo zvazvino uno kuti varwise vasingaregi masero ekenza.

Bottleneck yeCAR-T tekinoroji mune yakasimba mamota

However, the reason why it is effective in hematoma is because the tumarara cells of hematoma have an ancestral target-CD19 (only stored in tumor cells but not in normal cells), we can easily rely on this target Lead CAR-T cells to find cancer cells and eliminate cancer. A third CAR T-cell therapy targeting an antigen called BCMA is expected to be approved for akawanda myeloma (Bluebird) later this year. But there are not so obvious targets in solid tumors that exist only in cancer cells and not in normal cells.

Naizvozvo, masero eCAR-T anga asati ave nekiriniki inoshanda pakurapa mamota akasimba. Iyo yekurapa nharaunda yakagara ichivimba kuti maCAR T maseru anogona kukudziridza matsva akananga maturu kune mamwe akasimba mamota.

Kubudirira muCAR-T kurapwa kurwisa mamota akasimba

At present, with the change of CAR-T algebra, CAR-T has obvious improvements in proliferation and cytokine release. This technology has finally broken the ice, and more and more clinical trials have begun to try to use CAR-T for solid tumors. Treatment, patients with advanced solid tumors ushered in a warm spring!

Chaizvoizvo antigen zvinangwa zvinosanganisira:

Mesothelin, used to treat mesothelioma, pancreatic cancer, ovarian cancer, lung cancer; CEA, used to treat lung cancer, colon cancer, stomach cancer, breast cancer and pancreatic cancer; MUC-1, used to treat liver cancer, lung cancer , Pancreatic cancer, colon cancer, gastric cancer; GPC3, for the treatment of liver cancer; EGFRvII, for the treatment of gliomas, head and neck tumors; B7-H3, for the treatment of Ewing’s sarcoma, rhabdomyosarcoma, nephroblastoma, nerves Blastoma and medulloblastoma and brain stem tumors (DIPG), which are particularly difficult to treat;

PSMA, used for Kenza yeprotate, nezvimwe.

Claudin 18.2, used for gastric cancer, pancreatic cancer, Etc.

01 Mesothelin CAR-T

Mesothelin is a cell surface glycoprotein that is highly expressed in various tumors, such as malignant pleural mesothelioma, pancreatic cancer, ovarian kenza and some lung cancers, and is lowly expressed on the surface of normal pleura, peritoneum and pericardium. CAR-T cells against mesothelin have potential antitumor effects.

The latest results of mesothelin CAR-T therapy published by the University of Pennsylvania at the American Society of Clinical Oncology in 2019 show that a total of 6 patients with refractory metastatic pancreatic duct adenocarcinoma were successfully enrolled, and all patients have received 2 or more Multiple treatments. These patients were infused with mesothelin CAR T cells 3 times a week for a total of 9 doses. The results showed that there were 2 patients with stable disease, and their progression-free survival time was 3.8 months and 5.4 months.

Naizvozvo, iyi inorapa yekurapa iri biologically inoshanda mune varwere vane kenza yepancreatic, uye chidzidzo ichi chichiri mumakiriniki ekuedzwa (NCT03323944).

02 - B7-H3 "Pan kenza" CAR-T

Chikwata chaProfessor Majzner kubva kuStanford Medical College chakagadzira chizvarwa chitsva cheCAR-T kurapwa kwemamota akasimba. Izvi zvakakosha CAR T-Cell kurapa inorumbidzwa seimwe yemishonga inovimbisa zvikuru nekuti inovavarira B7-H3, mwero wepamusoro weantigen uripo mumamota mazhinji akasimba, kusanganisira mamwe kanzira dzehucheche.

They screened 388 children’s tumors for testing. The results showed that B7-H3 was present in 84% of the samples (tumor cells). B7-H3 content was very high in 70% of the samples. These include Ewing’s sarcoma, rhabdomyosarcoma, nephroblastoma, neuroblastoma and medulloblastoma, as well as brain stem tumors (DIPG) that are particularly difficult to treat.

Shure kwaizvozvo, Muzvinafundo Majzner nechikwata chake vakaumba chizvarwa chitsva cheCAR-T masero-B7-H3 CAR-T kuburikidza nehunyanzvi hwekugadzira jeni.

Pakarepo mushure meizvozvo, vaongorori vakatadza kumirira kuti vatange kuyedza pamakonzo. Vakaisa maseru ehunhu emunhu mumakonzo kuti vagadzire mbeva mhando dzekenza yehucheche. Aya mhando dzemakonzo dzakapihwa B7-H3 CAR T-Cell kurapa uye CD-19 CAR-T rinodzora boka, zvichiteerana.

Munhu wese akashamiswa! Muzvinafundo Majzner vakati: "Bundu rabva kunyangarika."

03, claudin18.2 MOTA-T

Mumakore maviri apfuura, mamota akasimba munyika medu akawana kubudirira kune mukurumbira pasi rese, uye bundu rekutanga rakasimba repasirese CAR-T kurapa yakanangana naClaudin 18.2 yakagadziriswa.

Claudin18.2. Kubva pane izvi, vaChinese vaongorori vakagadzira masero ekutanga eCAR-T epasi kurwisa Claudin 18.2.

Pamusangano we2019 ASCO wepagore, kiriniki yekuvandudzwa kweCAR-Claudin 18.2 T masero emukenza yemudumbu / wepancreatic yakaratidza kuti yakanangana neclaudin 18.2 CAR T maseru akashandiswa kurapa gumi nemaviri metastatic adenocarcinoma (12 kesi dzekenza yemudumbu uye 7 kesi dzepancreatic gomarara). Chiitiko chakakomba chakashata, kufa kwakanangana nekurapwa, kana neurotoxicity yakakomba yakaitika.

Pakati pezvinhu gumi nechimwe zvekuongorora:

1 kesi (gastric adenocarcinoma) yakasunungurwa zvachose;

3 kesi (gastric adenocarcinoma

2 zviitiko zvepancreatic adenocarcinoma, 1 kesi) kuregererwa zvishoma;

5 kesi dzaive dzakadzikama;

2 kesi dzakafambira mberi;

Iyo yakazara chinangwa chekupindura mwero yaive 33.3%.

Zvakare, CAR-Claudin 18.2 T masero ekutsvagisa kwekufungisisa nezvegomarara repamuviri akaratidzira kuti masero eCAR-T akanongedzerwa kuna Claudin 18.2 anogona kubvisa zvachose matumbo egastric mumakonzo emhando pasina chinokanganisa huturu.

The good news is that this trial has been pioneered by the Department of Gastroenterology and Oncology at Peking University Cancer Hospital, which is famous for mapundu emudumbu in China, to evaluate autologous humanized anti-claudin 18.2 chimeric antigen receptor T cells in advanced solid tumors. Safety and efficacy. Entry criteria (partial)

1. Makore gumi nemasere kusvika makumi manomwe nemashanu, murume kana mukadzi;

Vateereri vane hutachiona hwakasimbiswa mamota akasimba (kureva gomarara repamberi remudumbu, gomarara rekusangana, nekenza yepancreatic) vakatadza kurapwa kwakaringana;

3.Claudin 18.2 IHC ichisimbisa zvakanaka;

Hupenyu hunotarisirwa> masvondo gumi nemaviri;

MOTO T-Cell ekurapwa pakiriniki yekutsvaga

Pamusoro peichi chataurwa pamusoro pekufambira mberi kwekutsvagisa kwekiriniki, zvipatara zvikuru zvemumba parizvino zviri kuita kiriniki yeCAR-T pamusoro pemamota akasiyana.

Zvinodiwa nemurwere: Makore gumi nemasere- makumi masere ekuberekwa, anotarisirwa kurarama kweinenge mwedzi mitanhatu (kubva pekutanga ongororo yezvinhu kusvika pakupedzisa kwekurapa zvinotora mwedzi mishanu kusvika kumatanhatu), kazhinji ari muchimiro chakanaka, anokwanisa kugara ega.

Maitiro ekunyorera kweCAT T-Cell kutora

1. Kuongorora kwekutanga kwezvinhu: mushumo wechirwere, data yekuongorora mufananidzo mukati memwedzi mumwe, mushumo wezvino chiropa uye itsvo, pfupiso yekubudiswa kwechangobva kuendeswa kuCancerFax Medical Department;

2. Kutarisana-ne-kumeso kubvunzana: Murwere iye pachake akaunza zvese zviitiko zvemakiriniki kukiriniki yekutora chipatara zvakatarisana kumeso (nyaya yenyaya, kuburitsa pfupiso, kufungidzira mushumo firimu);

3. Immuno histochemical discovering: kuona tumor cell surface antigens EGFR, MUC1 uye mesothelin, imwe yacho yakasimba zvakasimba (yakakwirira kutaura) inogona kushanda kuCAR T-Cell therapy.

Kusati kwasvika kwesero therapy, mamota akasimba, anosanganisira advanced gastric adenocarcinoma uye pancreatic cancer, aiwanzo kurapwa nekuvhiyiwa uye radiotherapy uye chemotherapy. Chiitiko chegastric adenocarcinoma chaive chikamu che95% chegastric malignancies, uye gomarara repancreatic raive bundu rakajairika. Bundu rine dhigirii repamusoro, nguva yekupona kwepakati uye chiyero chemakore mashanu chekupona chakadzikira zvakanyanya kupfuura mamwe mapundu, anozivikanwa se "mambo wegomarara".

Nekudaro, vazhinji varwere vane kudzoka kwenzvimbo kana metastasis mushure mekuvhiyiwa. Mukuwedzera, rudzi urwu rwechirwere chakaipa hachinzwisisi kune radiotherapy uye chemotherapy. Naizvozvo, zvichibva pane yazvino standard kurapwa, iyo yekurapa mhedzisiro haina kukodzera, uye kufungidzira kwakanyanya kwazvo. Kuuya kwe immunotherapy kunounza tariro yakawanda uye mashura ekurarama kwenguva refu kune vakawanda varwere vemberi.

Isu tinotenda zvakasimba kuti mushure mekuunzwa kwema cellular immune immune system, nyika ichavhura musuwo kune cellular immunotherapy kubatsira varwere vegomarara, uye yedu nyika cellular immunotherapy ichave iri padanho repasi rose.

Unogona kuda kuverenga: CAR T-Cell kurapa muChina

FAQ iri paCAR T-Cell kurapa

Iko Car-T cell kurapa kunowanikwa here? Gomarara ripi rinonyanya kurapwa

A CAR-T cell immunotherapy has been akabvumidzwa by the US FDA for the treatment of leukemia and lymphoma. Nekudaro, kurapwa kwemamota akasimba haasati abvumidzwa uye parizvino ari mumakiriniki ekuedzwa

Masero eCar-T anogona here kurapa cancer yegastric?

mhinduro CAR-T yegomarara repamuviri parizvino iri kuongororwa kiriniki muBeijing Cancer. Varwere vanofanirwa kushandisa matissue zvikamu mukati megore rimwe kune boka rekuyedza kune yakatarwa tarisiro. Kana iyo bvunzo mhedzisiro iri yakanaka, saka

Pane here kuongororwa kwekiriniki kweCar-T maseru ekenza yemudumbu?

A Iko kune epamba kiriniki miedzo yeCAR-T yekenza yemudumbu, inoitwa kuPeking University Cancer Hospital. Varwere vanofanirwa kuve nehutachiona hutachiona zvikamu mukati megore rimwe kuitira kuongororwa kwezvakanangwa. Parizvino vakanyoreswa varwere

Vanogona kenza yechiropa varwere kutora chikamu muCAR-T kiriniki miedzo?

mhinduro According to your main complaint; the clinical application of CAR-T immunotherapy for solid tumors of gomarara rechiropa is not approved. The principle of CAR-T is to extract immune cells, and then use in vitro culture

Nyorera kuCAR T-Cell kurapwa

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